Virtual heart brings hope for rhythm disorder

By Ashley R. Smith

Fluid dynamics plays an integral
role in the propulsion of a jet
engine. Engineers know how the
properties of fluids — density,
pressure, temperature and velocity —
work in engines to achieve compression,
injection and thrust.

Jacques Beaumont, Watson School
assistant professor of bioengineering,
hopes to one day have that same level
of familiarity with biological tissues and
systems.

“When we design the engine of an
airplane today, the simulation is absolutely
phenomenal. It’s reliable to the
point where we have eliminated the need
for wind-tunnel tests,” Beaumont says.

Creating computer models of the
human heart is bringing that kind of
progress to medicine as well. “We can
simulate blood flow in an aneurism to
predict the risk of rupture,” he says. “Or
even simulate excitation of the heart.”

Beaumont uses modeling of the heart to
develop noninvasive methods for assessing
the risk of life-threatening arrhythmias.
He notes that one in 2,500 people lives
with a gene mutation that causes inherited
heart arrhythmia, a life-threatening
condition without a simple solution.

A healthy heart has a stable rhythm
set in motion by electrical signals.
When a mutation causes those electrical
impulses to malfunction, the
heart can beat irregularly.

Patients are typically diagnosed in
their early 20s when they first visit
a clinic complaining of weakness,
frequent nausea and, in severe cases,
syncope or a loss of consciousness.
“From that point on, they need to be
monitored very closely,” Beaumont
says. “If an episode of arrhythmia lasts
too long it can cause death.”

The particular mutations are often
difficult to diagnose as they can differ
from person to person. A certain
number of elements are common, but
variations in the mutation can cause
different triggers of arrhythmias.
For some patients, rapid changes in
adrenaline — caused by such things as
fear, anger or even the surprise of an alarm clock — can short-circuit their
heart’s rhythmic beating.

“When the field started in the
late 1980s, we had identified three
mutations that put an individual at risk.
Now we have 200,” Beaumont says.

But current treatment options are
unreliable. While there are a number of
drugs, Beaumont says their outcomes
vary widely. “What works for one patient
doesn’t necessarily work for the next.”

Another common treatment is the
use of an implantable cardioverterdefibrillator
(ICD). This device sends a
strong electrical shock to resynchronize the heart’s cells. However, “it has to
cover the entire volume of the heart,
so the shock has to be strong. When
you send a shock like this, you also
excite nerves, and that causes pain,”
Beaumont says.

“Every single shock produces pain.
And when there are a number of false
positives — we know it’s at least 20
percent — patients often elect to get
their ICD removed despite the risk of
cardiac death.”

As time passes, the probability of
dying from cardiac arrest increases exponentially. According to Beaumont,
by age 40, the probability of death for
symptomatic individuals is 80 percent.

Thus, he and PhD student Ashley
Raba ’07, MS ’09, are working to develop
computer-simulated testing methods
that will allow clinicians to assess the
cause of a person’s arrhythmia and
potentially cure it. If their research
proves definitive, current treatments
could be rendered unnecessary.

Once you know the mechanism,
the cure follows,” Beaumont says,
citing another heart condition known
as Wolff-Parkinson-White syndrome. Wolff-Parkinson is caused by an
extra electrical pathway in the heart
that results in severe arrhythmia in
young children and teenagers, limiting
their ability to exercise. But once the
problem was understood, finding a cure
was simple. “We now have a protocol to
stimulate the heart and, depending on
how the heart responds, we locate the
zone and apply radio frequency to scar
that tissue.” The children are cured.

For their research into inherited
arrhythmias, Beaumont and Raba are
developing a computer heart model that
will reconstruct an individual’s cardiac
beat by personalizing the building blocks
of the heart. “We know how human cells
generate electrical impulse, and we know
how they’re transmitted. The template
model can then be modified with information
collected clinically, including
images of the heart through CAT scan
and with message RNA through a blood sample,” Beaumont explains.

With this virtual heart, they will be
able to run large-scale simulations.

“The model will show where the
arrhythmia is initiated, what conditions
trigger it, and whether the patient will
respond to certain therapies,” Raba
explains.

“The modeling aspect of medicine
could change everything,” says Ron
Miles, Watson School associate dean for
research. “It’s an area that is hopeful,
but biological tissues are very different,
and this kind of research is extremely
difficult. But the promise is there.”